| Space Ace | Super Nintendo Entertainment System | 1994 | Oxford Digital Enterprises Ltd |
| Space Chimps | Wii | 2008 | Redtribe |
| Space Football: One on One | Super Nintendo Entertainment System | 1992 | Bits Studios |
| Space Harrier | Nintendo Entertainment System, Nintendo 3DS | 1985 | Sega AM2 |
| Space Hunter | Nintendo Entertainment System | 1986 | Kemco |
| Space Intervention | Nintendo 3DS | 2021 | — |
| Space Invaders | Nintendo Entertainment System, Super Nintendo Entertainment System, Game Boy | 1978 | Taito |
| Space Invaders DX | Super Nintendo Entertainment System | 1994 | — |
| Space Invaders Get Even | Wii | 2008 | Taito |
| Space Invaders: Fukkatsu no Hi | Wii | 1990 | Taito |
| Space Megaforce | Super Nintendo Entertainment System | 1992 | Compile |
| Space Raiders | Nintendo GameCube | 2002 | Taito |
| Space Shuttle Project | Nintendo Entertainment System | 1991 | Imagineering |
| Space Station Tycoon | Wii | — | Wahoo Studios |
| Spaceball Revolution | Wii | 2009 | Virtual Toys |
| Spanky's Quest | Super Nintendo Entertainment System, Game Boy | 1991 | Winning Entertainment Group |
| Sparkster | Super Nintendo Entertainment System | 1994 | Konami |
| Sparkster: Rocket Knight Adventures 2 | Super Nintendo Entertainment System | 1994 | Konami |
| Spartan X 2 | Nintendo Entertainment System | 1991 | Irem |
| Spartan: Total Warrior | Nintendo GameCube | 2005 | Creative Assembly |
| Spawn: Armageddon | Nintendo GameCube | 2003 | Point of View, Inc. |
| Spear of Destiny | Super Nintendo Entertainment System | 1992 | id Software |
| Special Jinsei Game | Nintendo GameCube | 2003 | Takara |
| Spectre | Super Nintendo Entertainment System | 1991 | — |
| Spectrobes: Origins | Wii | 2009 | Genki |
| Speed Challenge: Jacques Villeneuve's Racing Vision | Nintendo GameCube | 2002 | Ubisoft |
| Speed Kings | Nintendo GameCube | 2003 | Climax Studios |
| Speed Racer in My Most Dangerous Adventures | Super Nintendo Entertainment System | 1994 | Radical Entertainment |
| Speed Racer: The Videogame | Wii | 2008 | Sidhe |
| Speedball | Game Boy | 1988 | The Bitmap Brothers |
| Speedy Gonzales | Game Boy | 1993 | — |
| Speedy Gonzales: Aztec Adventure | Game Boy | 1999 | Sunsoft |
| Speedy Gonzales: Los Gatos Bandidos | Super Nintendo Entertainment System | 1995 | Sunsoft |
| Spellcraft: Aspects of Valor | Super Nintendo Entertainment System | 1992 | — |
| Spelunker | Nintendo Entertainment System | 1985 | MicroGraphic Image |
| Spelunker II: Yūsha e no Chōsen | Nintendo Entertainment System | 1987 | Now Production |
| Sphinx and the Cursed Mummy | Nintendo GameCube | 2003 | THQ Nordic, Eurocom |
| Spider-Man | Nintendo GameCube | 2002 | Treyarch, Gray Matter Interactive |
| Spider-Man 2 | Nintendo GameCube | 2004 | Treyarch |
| Spider-Man 3 | Wii | 2007 | Blizzard Albany, Treyarch |
| Spider-Man 3: Invasion of the Spider-Slayers | Game Boy | 1993 | Bits Studios |
| Spider-Man and the X-Men in Arcade's Revenge | Super Nintendo Entertainment System, Game Boy | 1993 | Software Creations |
| Spider-Man and Venom: Maximum Carnage | Super Nintendo Entertainment System | 1994 | Software Creations |
| Spider-Man Animated Series | Super Nintendo Entertainment System | 1995 | — |
| Spider-Man: Edge of Time | Nintendo 3DS, Wii | 2011 | Beenox |
| Spider-Man: Friend or Foe | Wii | 2007 | Next Level Games |
| Spider-Man: Return of the Sinister Six | Nintendo Entertainment System | 1992 | Bits Studios |
| Spider-Man: Shattered Dimensions | Wii | 2010 | Beenox |
| Spider-Man: Web of Shadows | Wii | 2008 | Shaba Games |
| Spindizzy Worlds | Super Nintendo Entertainment System | 1992 | — |
| Spirit Camera: The Cursed Memoir | Nintendo 3DS | 2012 | Koei Tecmo Holdings |
| Spirou | Super Nintendo Entertainment System | 1995 | Infogrames |
| Splatterhouse: Wanpaku Graffiti | Nintendo Entertainment System | 1989 | Now Production |
| SPOGS Racing | Wii | 2008 | Pronto Games |
| SpongeBob HeroPants | PlayStation Vita, Nintendo 3DS | 2015 | Behaviour Interactive |
| SpongeBob SquarePants featuring Nicktoons: Globs of Doom | Wii | 2008 | Incinerator Studios |
| SpongeBob SquarePants: Battle for Bikini Bottom | Nintendo GameCube | 2003 | Heavy Iron Studios |
| SpongeBob SquarePants: Creature from the Krusty Krab | Nintendo GameCube, Wii | 2006 | Blitz Games |
| SpongeBob SquarePants: Lights, Camera, Pants! | Nintendo GameCube | 2005 | THQ |
| SpongeBob SquarePants: Plankton's Robotic Revenge | Nintendo 3DS, Wii | 2013 | Behaviour Interactive |